The purpose of this K01 application is to support a period of didactic training and mentored research on the genetic epidemiology of childhood invasive pneumococcal disease (IPD). Dr. Mahon, who received her MD from UCSF, her MPH from DC Berkeley, and trained as an EIS officer in the Foodborne and Diarrheal Diseases Branch, has recently focused her career on vaccine-preventable diseases. Her position as Assistant Professor of Epidemiology and Pediatrics at the Boston University (BU) Schools of Public Health and Medicine has allowed her to draw upon two areas of research excellence at BU-childhood pneumococcal disease, which has been a decades-long focus within the Division of Pediatric Infectious Disease, and statistical genetics, in which the Department of Biostatistics has great depth and breadth. Her mentors, Stephen Pelton, MD and L. Adrienne Cupples, PhD, are the chief and chair of these groups, respectively. Dr. Mahon is seeking didactic and research training to expand upon her existing expertise in epidemiology in order to conduct studies of genetic factors involved in susceptibility to invasive pneumococcal disease (IPD) and in the protective response to the heptavalent pneumococcal conjugate vaccine (PCV7). She will conduct three studies of the role of candidate genes involved in pneumococcal disease and vaccine response using cases of childhood IPD detected through enhanced laboratory-based public health surveillance in Massachusetts. The first study is a family-based association study, conducted with cases and their families, of the association of the candidate genes with IPD. The second study is a case-control study, conducted with the same cases and with unrelated child controls with nasopharyngeal pneumococcal colonization, of the association of the same candidate genes with IPD. The third study examines the association of the candidate genes for PCV7 vaccine response with the occurrence of PCV7 failure, using both siblings of cases and unrelated colonized controls as comparison groups. Each study will control for possible confounders, such as underlying illness and tobacco smoke exposure. The ultimate goal of these projects is to improve understanding of why IPD continues to occur and to develop Dr. Mahon's capability to independently extend this research to address genetic issues in the control of vaccine-preventable diseases